Fig. 4: ROS as important mediators of immune cell signaling.

a G6PD is important for the generation of NADPH and ribose-5-phosphate (R5P). These molecules support several reductive biosynthetic pathways including fatty acid, amino acid and nucleotide biosynthesis. In turn, these processes support cellular growth and proliferation. G6PD-d therefore may hinder growth and proliferation. b ROS are generated by NADPH-dependent and NADPH-independent processes. For example, NADPH oxidases (NOX) generate NADPH-dependent ROS while mitochondrial membrane proteins (i.e. complexes I and III), peroxisomal β-oxidation, and various other enzymes generate NADPH-independent ROS. Glutathione and thioredoxin represent two important antioxidant molecules that resolve accumulated ROS and rely on a functional G6PD enzyme for regeneration. c ROS are generated upon engagement of several immune cell receptors including toll-like receptors (TLR), B cell receptors (BCR), and T cell receptors (TCR). ROS from different sources can affect protein phosphatases, kinases and transcription factors, ultimately altering several different signaling pathways. Examples of such signaling pathways, proteins or protein complexes that have been shown to be influenced by ROS include NFκB, MAPK, PI3K and NLRP3. Thus, ROS have the potential to influence immune cell function through modification of signaling. The examples included are not exhaustive.